质子泵抑制药药动学的研究进展

质子泵抑制药(PPIs)是临床中主要的抑酸药,奥美拉唑、埃索美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑等PPIs在药动学方面存在很大的差异(如生物利用度、代谢型、药物的相互作用、生物特异性等方面)。近年来,有很多文献报道了P450酶(CYP)代谢对PPIs的药动学影响。临床证据证明PPIs安全有效,但仍有很多患者对PPIs耐药,所以在实践中应该选择性应用PPIs。     

近年来质子泵抑制剂的研究进展

概述了质子泵抑制剂（PPIs)作为临床应用最广泛的抗酸药物的作用机制,以及各种不同PPIs包括奥美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑、莱米诺拉唑和吡帕拉唑等的临床应用特点。     

质子泵抑制剂注射剂型的稳定性和安全性

本文通过文献查新、阅读在线资料和国内外市售质子泵抑制剂PPIs产品说明书等资料,从辅料、稀释溶媒、室温稳定性等方面,对比各种注射用PPIs体外配伍稳定性和使用安全风险。发现我国上市销售的注射剂用PPIs产品包括奥美拉唑、兰索拉唑、泮托拉唑、埃索美拉唑;四种产品在葡萄糖注射液中的稳定性均不佳,配制后数小时内可发生颜色变化、有效成分降低和有关物质含量增加的情况;静脉滴注用和静脉注射用的PPIs剂型的辅料不同,混用会产生稳定性和血管刺激问题。在市售PPIs产品中,除商品名为"洛赛克"的奥美拉唑之外,均只能使用生理盐水稀释;不能混用静脉滴注用和静脉注射PPIs制剂,建议静脉滴注兰索拉唑时加用1.2μm过滤器。     

某三甲教学医院普通外科住院患者使用质子泵抑制剂预防应激性黏膜病变的调查分析

目的分析某三甲教学医院普通外科质子泵抑制剂(PPIs)的使用情况,指导普通外科合理使用PPIs。方法收集该院2016年9-12月普通外科住院患者病历,统计分析PPIs用于预防应激性黏膜病变(SRMD)的使用情况,从适应证、给药剂量、给药频次、溶剂及溶剂量、给药途径、给药时机、给药疗程等方面进行合理性评价。结果共收集511份病例资料,预防使用PPIs的有343份,使用率为67.1%。使用PPIs的患者中有适应证的240例,预防使用率为83.3%;无适应证的103例,预防使用率为46.2%;PPIs用于术后预防SRMD使用率为76.4%。其中结肠癌、直肠癌、胃癌等消化系统肿瘤的预防使用率高于静脉曲张及血栓形成、乳腺癌、甲状腺癌等疾病。预防使用PPIs药物中奥美拉唑的使用率高于泮托拉唑、兰索拉唑及埃索美拉唑;PPIs静脉给药占98.8%;PPIs给药疗程不适宜为30.3%。结论该院普通外科使用PPIs预防SRMD存在无适应证用药、给药途径不适宜、给药时机不适宜、疗程不适宜等现象。因此,需要加强PPIs使用管理,限制其预防用药指征,促进PPIs在普通外科的合理使用。     

某三甲医院抑酸剂的使用情况分析

目的系统分析西安市某三甲医院H2受体阻滞剂(H2RAs)和质子泵抑制剂(PPIs)的使用情况,为临床合理用药提供参考依据。方法从该院信息管理系统(HIS)中提取2017年H2RAs和PPIs的用药数据,计算用药频度(DDDs)和限定日费用(DDC)等药物经济学指标,进行回顾性分析。结果该医院使用抑酸剂99%以上是PPIs,几乎很少使用H2RAs。门诊患者使用口服抑酸剂的比例占93%,住院或急诊患者用静脉抑酸剂的比例占99%。PPIs全年的销售金额达到5 000多万元。其中静脉用药的销售金额为89%左右,使用量排名前3位的是兰索拉唑、泮托拉唑和雷贝拉唑,DDDs排名前3位的是兰索拉唑、泮托拉唑和奥美拉唑,DDC排序前3位的是雷贝拉唑(256.5元)、埃索美拉唑(118.23元)和兰索拉唑(84.8元)。口服PPIs用量排名前3位的是泮托拉唑、兰索拉唑和奥美拉唑,DDC排序前3位的是雷贝拉唑(26.84元)、埃索美拉唑(11.26元)和奥美拉唑(7.15元)。结论该三甲医院抑酸剂主要使用PPIs,静脉使用过多,销量较大的几种静脉用PPIs的DDC值较高,不符合社会性及经济性的需求。兰索拉唑与其他PPIs相比无优势,但销售金额占50%,存在滥用现象。建议进一步加强PPIs的点评机制,促进其安全、有效使用。     

2011年杭州地区12家医院质子泵抑制药用药合理性分析

目的：了解杭州地区12家医院2011年质子泵抑制药（PPIs）用药的现状及合理性。方法：采用金额排序、用药频度（DDDs）排序,了解该地区12家医院PPIs使用情况;制定PPIs合理用药评价标准,评价PPIs用药合理性。结果：该地区12家医院PPIs使用量泮托拉唑〉奥美拉唑〉埃索美拉唑镁〉雷贝拉唑〉兰索拉唑;PPIs处方数31 929张,不合理处方13 535张。不合理使用主要表现为用药指征不合理（60.53%）、用法不合理（17.63%）、用量不合理（9.46%）。结论：该地区PPIs使用存在较多不合理之处,建议颁布PPIs使用规范,同时加强监督管理,确保临床合理用药。     

质子泵抑制剂与急性间质性肾炎

质子泵抑制剂(proton pump inhibitors,PPIs)致急性间质性肾炎(acute interstitial nephritis,AIN)是一种罕见而严重的药物不良事件.目前临床使用的PPIs如奥美拉唑、埃索美拉唑、泮托拉唑、雷贝拉唑和兰索拉唑都可致AIN,其中以奥美拉唑报道最多.PPIs致AIN的临床...     

老年消化性溃疡患者长期应用质子泵抑制剂对骨质疏松的影响

<正>质子泵抑制剂(PPIs)是一类作用于胃H+-K+ATP酶的强效抑酸药,临床常用药物包括奥美拉唑、兰索拉唑、埃索美拉唑、泮托拉唑及雷贝拉唑等~([1])。传统认为,PPIs用于治疗幽门螺旋杆菌相关的消化性溃疡疾病,不良反应轻微,部分患者可以长期服用此类药物对病情进行控制。近期有研究表明,患者长期使用PPIs后,可影响维生素及钙的吸     

2012-2016年西安市第一医院质子泵抑制剂的使用情况分析

目的 对2012-2016年西安市第一医院质子泵抑制剂（PPIs）的使用情况进行分析,为临床合理用药提供参考。方法 采用回顾性方法,对2012-2016年西安市第一医院PPIs的销售金额、用药频度（DDDs）、日均费用（DDC）和排序比（B/A）等进行统计分析。结果 2012-2016年,PPIs的销售金额呈逐年增长的趋势;门诊和住院患者PPIs的销售金额、DDDs整体呈增加趋势;口服PPIs的销售金额和DDDs分别占24.4%、71.3%;注射用PPIs的销售金额和DDDs占比分别为75.6%、28.7%;5年来销售金额排名前3位的是注射用泮托拉唑（40 mg）、注射用兰索拉唑和雷贝拉唑钠肠溶片;DDDs排名前3位的是兰索拉唑肠溶片、雷贝拉唑钠肠溶片和注射用泮托拉唑（40 mg）。奥美拉唑肠溶胶囊、兰索拉唑肠溶片和泮托拉唑肠溶胶囊的DDC在5年中均小于10元。注射用兰索拉唑和注射用泮托拉唑（40 mg）5年的B/A均小于1.00。消化科PPIs的用药金额始终为第1位。结论 西安市第一医院注射用泮托拉唑的用量相对较大,可能存在一定程度的过度用药和不合理用药。     

伊曲康唑胶囊与PPIs类药物在PK/PD方面的影响

文章旨在研究伊曲康唑胶囊与质子泵抑制剂(PPIs)类药物之间的相互作用以及不可避免联用时的优化方案。通过搜索pubmed、中国知网、百度学术等数据库查找伊曲康唑口服剂型(胶囊、口服液)与PPIs相互作用的研究,评估相互作用带来的负效应解决方案。研究结果显示,PPIs类药物会严重减少伊曲康唑胶囊的吸收,应尽量避免联用,但对伊曲康唑口服液的吸收无显著影响。若伊曲康唑胶囊与PPIs类药物却有同时使用的用药指征,可考虑与酸性饮料如可乐同服,或者用伊曲康唑口服液剂型代替胶囊剂型。临床药师应提醒临床对此相互作用引起重视,若出现不可避免的联用应结合患者自身情况包括经济能力、基础疾病、合并用药等进行方案优化,真正实现用药个体化。     

Comparison of the gastrointestinal anatomy,physiology, and biochemistry of humans and commonly used laboratory animals

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.     

miR-15b基因干扰在脑缺血再灌注损伤中的作用及机制研究

目的 探讨微小核糖核酸-15b(miR-15b)基因干扰对脑缺血再灌注损伤的影响及其作用机制。方法 取新生24 h内Wistar乳鼠的大脑皮层星形胶质细胞传代培养并鉴定,氧糖剥夺/再恢复法处理模拟体内脑缺血再灌注损伤（模型组）;无特殊处理的大脑皮层星形胶质细胞为对照组。构建miR-15b干扰腺病毒载体及阴性对照载体,分别转染上述模型组细胞,记为过表达组、沉默组、过表达对照组、沉默对照组,另设置空白组。24 h后,倒置相差显微镜观察各组细胞形态学改变;氮兰四唑盐（MTS）法检测细胞存活率,乳酸脱氢酶（LDH）漏出率实验检测细胞活力;流式细胞术检测细胞凋亡率;实时荧光定量聚合酶链反应检测各组细胞miR-15b以及B淋巴细胞瘤-2(Bcl-2)、胱天蛋白酶-3(Caspase-3)、Caspase-9 mRNA表达;Western blot检测各组细胞Bcl-2、Caspase-3、Caspase-9蛋白表达;荧光素酶报告基因实验验证miR-15b是否靶向调控Bcl-2。结果 与对照组比,空白组、过表达对照组和沉默对照组贴壁细胞减少,细胞缩小变圆,分布松散,细胞存活率和Bcl-2 mRNA及...     

Stakeholders in Opioid Substitution Treatment Policy: Similarities and Differences in Six European Countries

Based on the research papers within this special issue, this overview discusses similarities and differences in stakeholding in drug user opioid substitution treatment policy in Britain, Denmark, Italy, Austria, Poland, and Finland. It explores factors that have influenced stakeholder activity, including the importance of crisis, the impact of evidence, the availability of resources, the wider political context, the influence of moral frameworks and ideologies, and the pressure of external influences. The paper highlights the important differences in the emergence and evolution of stakeholder groups and in the political, cultural, and economic circumstances, which both constrain and enable their activities.     

基于HMGR、SQS1、β-AS基因CNVs的甘草道地性机制研究

本文利用real-time PCR方法对不同产地甘草的3-羟基-3-甲基戊二酰CoA还原酶 (3-hydroxy-3-methylglutaryl-CoA reductase, HMGR)、鲨稀合成酶1 (squalene synthetase 1, SQS1)、β-香树脂醇合成酶 (β-amyrin synthase, β-AS) 基因的拷贝数进行了研究, 发现不同产地的HMGR基因存在1～3个拷贝数变异, SQS1基因存在1～2个拷贝数变异, 未发现β-AS基因拷贝数变异。甘草HMGR、SQS1、β-AS基因拷贝数存在5种自然组合类型: A型 (2+1+1)、B型 (1+1+1)、C型 (3+2+1)、D型 (2+2+1) 和E型 (3+1+1), 其中内蒙古杭锦旗甘草存在A、B两种类型, A与B的比例为1∶1.3; 内蒙古赤峰甘草也存在A、B两种类型, 但A与B比例为3∶1; 宁夏盐池甘草存在A、B、C、D 4种类型, A/B/C/D比例为1∶5.1∶1∶2, A/B比例为1∶5.1; 甘肃民勤甘草存在A、B、E 3种类型, A/B/E比例为4.1∶2.1∶1, A/B比例为2∶1。本研究证明中药功能基因基因组拷贝数变异 (copy number variations, CNVs) 与产地具有相关性, 可能是道地药材形成的机制之一。     

Effects of typical and atypical antipsychotics on glucose–insulin homeostasis and lipid metabolism in first-episode schizophrenia

Rationale Glucose and lipid metabolism dysfunction is a significant side effect associated with antipsychotics. Although there are many studies about the linkages between drugs and metabolic dysfunction, most of these studies have compared the effects of two antipsychotics on only one metabolic measure: either glucose or lipid metabolism.Objectives The present study aimed to investigate the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and lipid metabolism in first-episode schizophrenia.Materials and methods One hundred twelve schizophrenics were assigned randomly to receive clozapine, olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide, insulin resistance index (IRI), cholesterol, and triglyceride. All measures were collected at baseline and at the end of the 8-week treatment.Results After treatment, insulin, C-peptide, and IRI were significantly increased in the four groups, but not fasting glucose levels. Cholesterol and triglyceride levels were significantly increased in the clozapine and olanzapine groups. Patients treated with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI levels than those treated with risperidone and sulpiride. Among the four antipsychotics, the increases of mean BMI from high to low were as follows: clozapine, olanzapine, sulpiride, and risperidone.Conclusions This study confirmed that the four antipsychotic drugs were associated with an increase of insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were associated with an increase in cholesterol and triglyceride levels. The effects of clozapine and olanzapine on the glucose and lipid metabolism outweighed those of risperidone and sulpiride.     

Molecular pathology of drug-disease interactions in chronic autoimmune inflammatory diseases

The aetiology of autoimmune, chronic inflammatory disease is reviewed, together with the contributing roles of oxygen radicals, the cytochromes P450, the eicosanoids, the interleukins, and the corticosteroids and estrogens. The importance of drug metabolism in the formation of reactive intermediates of drugs and environmental chemicals, and hence in the production of neoantigens, autoantibodies and autoimmune disease is considered, together with the possible involvement of genetic variations in sulphoxidation, sulphotransferase and acetyltransferase activities in predisposing patients to rheumatoid arthritis, lupus and other autoimmune diseases. The toxicity of anti-inflammatory drugs, and the molecular mechanisms involved, are reviewed, including the formation of neoantigens and autoantibodies by the acylation of proteins by ester glucuronide metabolites of non-steroidal anti-inflammatory drugs, by the formation of disulphide protein conjugates of penicillamine, by theN-oxygenation of sulphonamides, and the oxygenation of hydralazine, procainamide and other drugs by leukocyte NADPH-oxidase and myeloperoxidase. The limitations of the existing procedures for the safety evaluation of new drugs, and their inability to identify potential immunotoxicity in man, are considered, and the advantages of the molecular structure procedure of COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity), and the enzyme induction procedure of ENACT (Enzyme Induction Analysis for Chemical Toxicity), for identifying potential carcinogenic and immunotoxic chemicals, are briefly discussed.     

无痛可视人工流产术有效性安全性相关因素研究

目的：研究探索无痛可视人工流产术有效性与安全性之间的相关因素。方法：比较五组麻醉药（瑞芬太尼、瑞芬太尼＋丙泊酚、瑞芬太尼＋咪唑安定、丙泊酚、丙泊酚＋芬太尼）作用时间、止痛效果、副反应及对体温、呼吸、脉搏、血压及血氧饱和度的影响等,严格操作规范,完善各环节工作,总结有效性与安全性之间的相关因素。结果：五组麻醉药中对诱导、手术、苏醒时间和定向力恢复时间以瑞芬太尼＋丙泊酚组最佳,镇痛效果显著,差异具有统计学意义,P〈0．05：对生命指征的影响以瑞芬太尼＋丙泊酚组最小,安全系数最高,经统计学处理．P〈0．05。瑞芬太尼＋丙泊酚最佳用药量分别为0．9-1．4ug／kg、1．9—2．2mg／kg。无痛可视人工流产术有效性与安全性之间的相关因素有：手术适应证、全麻药组合及剂量的选择、施术环境及设备的配置、受术者知情同意、手术医生、护士和麻醉医师的责任心及技术水平、术后指导及随访等。结论：无痛可视人工流产术有效性安全性与手术适应证、全麻药组合及剂量的选择、施术环境及设备的配置、受术者知情同意、手术医生、护士和麻醉医师的责任心及技术水平、术后指导及随访等因素有关。     

检验检测机构化学试剂QC实验室的关键要素分析

目的：验证实验试剂的质量,为检验工作选择符合要求的化学试剂提供数据依据。方法：对QC实验室成立以来已完成的2批常用化学试剂的检测情况进行总结,并对样品、人员、仪器设备、实验材料、方法标准、环境等6个控制要素进行分析。结果与结论：检验检测机构所使用的实验材料品质,是影响其工作结果的重要因素,建立质量控制实验室（QC实验室）并进行化学试剂质量控制具有重要意义,便于筛选合格供应商,指导并规范实验用试剂及耗材的采购,从而进一步满足食品药品各项检验检测工作的需要,确保检验检测数据与结论的公正性、有效性。     

藏药佐太的抗抑郁抗焦虑作用研究

目的 观察藏药佐太的抗抑郁和抗焦虑作用,并探讨其可能作用机制。方法 1）初步评价实验：在小鼠ig给予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通过强迫游泳实验和开场实验初步评价佐太对抑郁和焦虑的影响,同时通过检测小鼠血清中5-羟色胺（5-HT）和去甲肾上腺素（NE）水平来探讨佐太产生影响的可能作用机制。2）不可预测性慢性温和应激模型（CUMS）实验：建立CUMS模型,ig给予6.07、60.70、606.97 mg/kg佐太后,通过小鼠体质量变化、糖水偏爱实验、小鼠悬尾实验、开场实验和埋珠实验评价佐太对CUMS模型小鼠的抗抑郁和抗焦虑作用,同时检测小鼠血清中皮质酮（CORT）、促肾上腺皮质激素（ACTH）和下丘脑中促肾上腺皮质激素释放激素（CRH）水平,测定佐太对CUMS模型小鼠下丘脑-垂体-肾上腺（HPA）轴的影响。结果 1）佐太能够显著减少小鼠强迫游泳实验中不动时间（6.07、60.70、303.49、606.97 mg/kg）;增加小鼠在开场实验中中央区停留时间百分率（606.97 mg/kg）和中央区运动百分比（303.49、606.97 mg/kg）;增加小鼠血清中5-HT（6.07、606.97 mg/kg）和NE（6.07、303.49、606.97 mg/kg）水平。2）CUMS实验中,与对照组比较,经过42 d CUMS慢性应激小鼠表现出明显的抑郁和焦虑样行为,包括糖水偏爱率的降低、悬尾不动时间显著增加、开场实验中运动时间、中央区域停留时间及运动距离的减少和周边区域运动距离的增加、埋珠实验中埋珠个数的增加。而ig给予佐太（6.07、60.70、606.97 mg/kg）能够显著改善CUMS模型引起的上述症状,并且佐太（6.07、60.70 mg/kg）能够显著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA轴亢进。结论 佐太具有一定的抗抑郁和抗焦虑作用,并且其作用机制可能与升高5-HT、NE水平和抑制HPA轴亢进有关。     

The development of environmentally acceptable fluorocarbons

Abstract

Chlorofluorocarbons (CFCs) were introduced in the 1930s as the safe replacements for the toxic and flammable refrigerants being used at that time. Subsequently, hydrochlorofluorocarbons (HCFCs) were also developed. In addition to refrigerant applications, they were used as foam blowing agents, as solvents and as propellants for many aerosols. In the 1970s and 1980s, concern developed about their environmental impact, specifically on stratospheric ozone depletion. Industry began to consider acceptable replacements. In 1987, many of the governments of the world came together and drafted the Montreal Protocol, calling upon Industry to initially phase out production of the CFCs and later HCFCs. Within 4?months of the signing of the Montreal Protocol, the 15 global major producers joined together to form the Alternative Fluorocarbons Environmental Acceptability Study (AFEAS), which sponsored research into environmental effects and the Program for Alternative Fluorocarbons toxicity Testing, PAFT), which examined the toxicology of potential replacements for the CFCs and HCFCs. Nine replacements were identified by companies and, through this international cooperation; toxicology programs were designed, conducted, and evaluated without duplication of effort and testing; consequently these new products were introduced within less than 10?years. Indeed the Montreal Protocol has been recognized as the most appropriate international treaty to phase-down HFCs. In 2016 the Kigali Amendment to the Montreal Protocol set out a phase-down schedule for the consumption and production of HFCs. In order to reduce the consumption and emissions of high GWP HFCs. Recently lower GWP HFCs and very low GWP HFOs (hydrofluoroolefins and HCFOs (hydrochlorofluoroolefins) have been introduced into a range of applications. Summaries of the toxicology profiles of some of the original CFCs and HCFCs, the replacements and the new post-PAFT replacements are described. The chemicals in this review include CFC-11, CFC-12, CFC-113, CFC-114, HCFC 22, HCFC-123, HCFC-124, HCFC-141b, HCFC-142b, HCF-32, HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-245ea, HFC-245fa, HFO-1234yf, HFO-1234ze, and HCFO-1233zd.